PUBLICATION
Follow that cell: leukocyte migration in L-plastin mutant zebrafish
- Authors
- Linehan, J.B., Zepeda, J.L., Mitchell, T.A., LeClair, E.E.
- ID
- ZDB-PUB-220712-7
- Date
- 2022
- Source
- Cytoskeleton (Hoboken, N.J.) 79(4-5): 26-37 (Journal)
- Registered Authors
- LeClair, Elizabeth E.
- Keywords
- actin, cytoskeleton, immunity, macrophage, neutrophil, zebrafish
- MeSH Terms
-
- Actins*
- Animals
- Calcium
- Cell Movement/genetics
- Chemokines
- Integrins
- Leukocytes
- Mammals
- Membrane Glycoproteins
- Microfilament Proteins
- Zebrafish*/genetics
- PubMed
- 35811499 Full text @ Cytoskeleton
Citation
Linehan, J.B., Zepeda, J.L., Mitchell, T.A., LeClair, E.E. (2022) Follow that cell: leukocyte migration in L-plastin mutant zebrafish. Cytoskeleton (Hoboken, N.J.). 79(4-5):26-37.
Abstract
Actin assemblies are important in motile cells such as leukocytes which form dynamic plasma membrane extensions or podia. L-plastin (LCP1) is a leukocyte-specific calcium-dependent actin-bundling protein that, in mammals, is known to affect immune cell migration. Previously, we generated CRISPR/Cas9 engineered zebrafish lacking L-plastin (lcp1-/-) and reported that they had reduced survival to adulthood, suggesting that lack of this actin-bundler might negatively affect the immune system. To test this hypothesis, we examined the distribution and migration of neutrophils and macrophages in the transparent tail of early zebrafish larvae using cell-specific markers and an established wound-migration assay. Knockout larvae were similar to their heterozygous siblings in having equal body sizes and comparable numbers of neutrophils in caudal hematopoietic tissue at two days post-fertilization, indicating no gross defect in neutrophil production or developmental migration. When stimulated by a tail wound, all genotypes of neutrophils were equally migratory in a two-hour window. However for macrophages we observed both migration defects and morphological differences. L-plastin knockout macrophages (lcp1 -/-) still homed to wounds but were slower, less directional and had a star-like morphology with many leading and trailing projections. In contrast, heterozygous macrophages lcp1 (+/-) were faster, more directional, and had a streamlined, slug-like morphology. Overall, these findings show that in larval zebrafish L-plastin knockout primarily affects the macrophage response with possible consequences for organismal immunity. Consistent with our observations, we propose a model in which cytoplasmic L-plastin negatively regulates macrophage integrin adhesion by holding these transmembrane heterodimers in a 'clasped', inactive form and is a necessary part of establishing macrophage polarity during chemokine-induced motility. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping